Conference Coverage
Evolocumab halved cardiovascular events in OSLER study
Key clinical point: Evolocumab shows impressive LDL lowering and slashes cardiovascular events.
This month, Amgen expects to complete enrollment of FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a CV outcomes study of about 27,500 patients, which started in 2013 and should end by 2017. This also will provide safety data in more than 5,000 patients with LDL-C levels below 40 mg/dL, according to Amgen’s briefing documents posted on the FDA website before the meeting.
The Amgen data include four 12-week double-blind randomized studies comparing evolocumab to placebo or ezetimibe in about 3,100 patients. Both dosing regimens resulted in significantly lower LDL-C levels from baseline, compared with placebo and ezetimibe.
In studies of over 6,000 patients with primary hyperlipidemia or mixed dyslipidemia, evolocumab resulted in LDL-C reductions of 55%-75% compared with placebo, and 35%-45% compared with ezetimibe, according to Amgen. In studies of patients with homozygous familial hypercholesterolemia (HoFH), treatment was associated with LDL-C reductions of about 30%, compared with placebo. To date, no safety risk has been identified with low LDL-C levels in patients with levels that dropped below 25 mg/dL or 40 mg/dL, compared with levels of 40 mg/dL or greater, according to the company.
The proposed indication for evolocumab includes treatment of adults with hyperlipidemia or mixed dyslipidemia. Treatment would be in combination with a statin or a statin with other lipid-lowering therapies, or alone, or in combination with other lipid-lowering therapies in patients who are statin intolerant, or alone or in combination with other lipid-lowering therapies in patients for whom a statin is not considered clinically appropriate. It also is being reviewed for treatment of patients with HoFH who are aged 12 years and older in combination with other lipid-lowering therapies. The recommended doses for adults with primary hyperlipidemia and mixed dyslipidemia are 140 mg every 2 weeks or 420 mg once a month; 420 mg every 2 or 4 weeks is recommended for those with HoFH.
If approved, Sanofi and Regeneron plan to market alirocumab as Praluent and Amgen plans to market evolocumab as Repatha.